Although morphine is widely used in the newborn, its pharmacokinetics and metabolic fate are not well studied in this age group. Such data are critical for the rational use of this drug in acutely ill infants, particularly the preterm babies. Therefore, the longterm objectives of these studies are to develop standardized dosage regimens for morphine use, based on its clinical efficacy, pharmacokinetics, and metabolic data in newborn infants of various gestational and postnatal ages. The specific aims of this proposal are: 1) to show that morphine elimination half-life decreases and clearance increases in a predictable manner with increasing gestational and postnatal ages; 2) to study the alterations in morphine metabolism with increasing maturity; and 3) to identify the major metabolic pathways of morphine at different gestational and postnatal ages. Infants will be enrolled into either of the two phases of this protocol (total n = 132). Morphine pharmacokinetics will be studied in Phase I, and its metabolism will be studied in Phase II. In one half of each phase (Studies A), the effects of gestational age will be evaluated, and in the other half (Studies B), the effects of postconceptional age will be evaluated. The infant enrollment will be as follows: Phase I, Study A: (n = 30), age <5 days, and gestational age 25-40 weeks; Phase I, Study B: (n = 36), gestational age 25-40 weeks and postnatal age 2-8 weeks. The sample size assignment will be relatively uniform across 27-42 weeks postconceptional ages (3-4 infants each at 27-29 and 38-42 week postconceptional age brackets, and 6-7 infants each at 30-33 and 34-37 weeks postconceptional age brackets). In Studies A and B of Phase II, the enrollment pattern, including the sample size assignment, will be identical to that of Phase I. Plasma morphine levels will be measured using a radioimmune assay technique in phase I, and morphine, morphine-3-glucuronide, morphine-6-glucuronide, morphine ethereal sulphate, normorphine, and codeine will be measured in plasma and urine using a HPLC technique in phase II. The results of these studies will help in developing pharmacokinetic and physiologic rationale for the clinical use of morphine in the newborn period, and to minimize its side effects.